TY - JOUR
T1 - Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease
AU - International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium
AU - Blauwendraat, Cornelis
AU - Kia, Demis A.
AU - Pihlstrøm, Lasse
AU - Gan-Or, Ziv
AU - Lesage, Suzanne
AU - Gibbs, J. Raphael
AU - Ding, Jinhui
AU - Alcalay, Roy N.
AU - Hassin-Baer, Sharon
AU - Pittman, Alan M.
AU - Brooks, Janet
AU - Edsall, Connor
AU - Chung, Sun Ju
AU - Goldwurm, Stefano
AU - Toft, Mathias
AU - Schulte, Claudia
AU - Hernandez, Dena
AU - Singleton, Andrew B.
AU - Nalls, Mike A.
AU - Brice, Alexis
AU - Scholz, Sonja W.
AU - Wood, Nicholas W.
AU - Noyce, Alastair J.
AU - Tucci, Arianna
AU - Charlesworth, Gavin
AU - Tan, Manuela
AU - Houlden, Henry
AU - Morris, Huw R.
AU - Plun-Favreau, Helene
AU - Holmans, Peter
AU - Hardy, John
AU - Bras, Jose M.
AU - Quinn, John
AU - Mok, Kin Y.
AU - Billingsley, Kimberley
AU - Lewis, Patrick
AU - Guerreiro, Rita
AU - Lovering, Ruth
AU - Ogalla, Raquel Duran
AU - R’bibo, Lea
AU - Ryten, Mina
AU - Escott-Price, Valentina
AU - Chelban, Viorica
AU - Foltynie, Thomas
AU - Sheerin, Una Marie
AU - Williams, Nigel
AU - Danjou, Fabrice
AU - Corvol, Jean Christophe
AU - Lubbe, Steven
AU - Mencacci, Niccolo E.
N1 - Funding Information:
The authors would like to thank all members of the IPDGC ( http://pdgenetics.org/partners ) and COURAGE-PD consortia for proving data, support, and comments. This work was supported (in part) by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; projects 1ZIA-NS003154-2 and Z01-AG000949) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org .
Funding Information:
Dr. Mike A. Nalls' participation is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging, NIH, Bethesda, MD, USA. He also consults for Illumina Inc, the Michael J. Fox Foundation, and University of California Healthcare.
Publisher Copyright:
© 2017
PY - 2018/4/1
Y1 - 2018/4/1
N2 - SNCA missense mutations are a rare cause of autosomal dominant Parkinson's disease (PD). To date, 6 missense mutations in SNCA have been nominated as causal. Here, we assess the frequency of these 6 mutations in public population databases and PD case-control data sets to determine their true pathogenicity. We found that 1 of the 6 reported SNCA mutations, His50Gln, was consistently identified in large population databases, and no enrichment was evident in PD cases compared to controls. These results suggest that His50Gln is probably not a pathogenic variant. This information is important to provide counseling for His50Gln carriers and has implications for the interpretation of His50Gln α-synuclein functional investigations.
AB - SNCA missense mutations are a rare cause of autosomal dominant Parkinson's disease (PD). To date, 6 missense mutations in SNCA have been nominated as causal. Here, we assess the frequency of these 6 mutations in public population databases and PD case-control data sets to determine their true pathogenicity. We found that 1 of the 6 reported SNCA mutations, His50Gln, was consistently identified in large population databases, and no enrichment was evident in PD cases compared to controls. These results suggest that His50Gln is probably not a pathogenic variant. This information is important to provide counseling for His50Gln carriers and has implications for the interpretation of His50Gln α-synuclein functional investigations.
KW - H50Q
KW - His50Gln
KW - Parkinson's disease
KW - SNCA
UR - http://www.scopus.com/inward/record.url?scp=85041606064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041606064&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2017.12.012
DO - 10.1016/j.neurobiolaging.2017.12.012
M3 - Article
C2 - 29398121
AN - SCOPUS:85041606064
SN - 0197-4580
VL - 64
SP - 159.e5-159.e8
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -